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Abstract Objective: Nodular goiter may increase the risk of thyroid cancer, but the genetic factors contributing to nodular goiter are not well understood. There is an overexpression of H19 lncRNA in goiter tissue and its target remains unknown. In this study, we attempted to identify a new target for H19 in the context of goiter development. Methods: Using interaction energy calculations, the interaction between NKX2-1 mRNAand H19 lncRNA was examined. Putative microRNAs were found at the H19 lncRNA target site with the highest affinity for NKX2-1. RNAseq data was analyzed to determine the tissue specificity of gene expression. Samples were taken from 18 goiter and 18 normal tissues during thyroidectomy. The expression of NKX2-1 was determined by RT-qPCR using specific primers. Results: The interaction between NKX2-1 and H19 was characterized by six local base-pairing connections, with a maximum energy of –20.56 kcal/moL. Specifically, the sequence that displayed the highest affinity for binding with H19 overlapped with the binding site of has-miR-1827 to NKX2-1. It was found that NKX2-1 is exclusively co-expressed with H19 in normal thyroid tissue. As compared to adjacent normal tissues, nodular goiter tissues have a significant overexpression of NKX2-1 (relative expression = 1.195, p = 0.038). Conclusion: NKX2-1 has been identified as the putative target of H19 lncRNA, which is overex-pressed in nodular goiter tissues significantly. Level of Evidence: 4.

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Abstract Objectives: The role of Epoxide Hydrolase-4 (EPHX4), a member of epoxide hydrolase family, has not been investigated in cancer. The purpose of this article is to explore the application value of EPHX4 in laryngeal cancer and its relationship with immune infiltration. Methods: We observed that EPHX4 expression and its survival assays in laryngeal cancer specimens based on The Cancer Genome Atlas (TCGA) cohorts. We also analyzed the correlation between immune cell infiltration levels and EPHX4 gene copy number in laryngeal cancer. Finally, we conducted in vitro assay to evaluate the functions of EPHX4 in laryngeal cancer cell line. Results: EPHX4 is highly expressed in laryngeal cancer specimens and has a poor prognosis. EPHX4 related immune cell analysis showed that it participated in NK Natural killer cell mediated cytotoxicity. Finally, Cell experiments indicate that EPHX4 could promote laryngeal cancer cell line proliferation, colony formation and invasion. Conclusions: Our research results suggest that EPHX4 may be a potential immunotherapy target for laryngeal cancer. The nominated immune signature is a helpful and promising prognostic indicator in laryngeal cancer. Levels of Evidence: Level 3.

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Abstract Objective: A retrospective analysis was performed to explore the clinical effect of the Posterior Nasal Nerve (PNN) resection combined with hormone transnasal nebulization on Difficult-to-Treat Rhinosinusitis (DTRS). Methods: A total of 120 DTRS patients were selected and divided into a control group (n = 60) and a study group (n = 60) according to different treatments. The control group patients were treated via PNN resection, followed by normal saline transnasal nebulization; the study group patients were given PNN resection and then treated with budesonide suspension transnasal nebulization. Subsequently, the comparison was performed between the two groups in terms of (1) Clinical baseline characteristics; (2) Sino-nasal Outcome Test (SNOT)-22 scores before treatment and after 3-months, 6-months and 12-months of treatment; (3) Lund-MacKay scores before treatment and after 10, 30, 90, and 180 days of treatment; (4) Incidence of adverse reactions during treatment. Results: There was no significant difference in SNOT-22 or Lund-Kennedy scores between the two groups before treatment (p > 0.05). After treatment, the SNOT-22 and Lund-Kennedy scores of the control and the study groups were decreased, and compared with the control group, the SNOT-22 and Lund-Kennedy scores in the study group improved more significantly (p < 0.05). In addition, the study group and the control group presented with 1 and 4 cases of nasal adhesion, 2 and 3 cases of epistaxis, 1 and 4 cases of sinus orifice obstruction, 1 and 3 cases of lacrimal duct injuries, respectively. The incidence of adverse reactions in the study group was significantly lower than that in the control group (8.3% vs. 23.3%) (p < 0.05). Conclusion: PNN resection combined with hormone transnasal nebulization treatment can improve the symptoms and quality of life of DTRS patients, with good clinical efficacy but few adverse reactions. Therefore, such combination treatment deserves a promotion and application clinically. Level of Evidence: Level 3.

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Abstract Objectives: To determine the benefits of cochlear implantation in hearing loss children with multiple disabilities (MD) in terms of auditory outcomes, speech performance, and their quality of life. Methods: This was a cross sectional study from January 2019 to December 2020 in which thirty-one children with hearing loss and multiple disabilities were evaluated. Their improvement in auditory and speech performances were assessed using Categories of Auditory Performance version II (CAP-II) and the Speech Intelligibility Rating (SIR) scales. The assessment was done at 6-month intervals, with the baseline evaluation done at least six months after activation of the implant. Parents were asked to fill the Parents Evaluation of Aural/Oral Performance of Children (PEACH) diary and Perceived Benefit Questionnaire (PBQ) to evaluate the child’s quality of life. Results: All 31 children have Global Developmental Delay (GDD), with 11 having an additional disability. Both mean CAP-II and SIR scores showed significant improvement with increased hearing age (p < 0.05) after 6-month intervals. In addition, 20 out of 31 children (64.5%) have achieved verbal communication after implantation. The mean PEACH score in quiet was significantly better than in noise (p = 0.007) and improved with the increased of hearing age. The majority of parents (96%–100%) perceived a cochlear implant as beneficial to their child in terms of auditory response, awareness, interaction, communication, and speech development. Conclusions: Cochlear implantation had shown benefits in children with multiple disabilities. Outcome measures should not only focus on auditory and speech performances but the improvement in quality of life. Hence, individualized each case with realistic expectation from families must be emphasized in this group of children. Level of evidence: Level 3.

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Abstract Objectives: The purpose of this study is to investigate the lung function in Chronic Rhinosinusitis (CRS) patients with Chronic Cough (CC). Methods: A total of 1413 CC patients were retrospectively screened and 109 CRS patients with CC were enrolled. Lung function, Lund-Mackay Computed Tomography (CT) score, smoking status, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples, and Sino-Nasal Outcome Test were examined. Normal control subjects are also recruited. Results: The Forced Expiratory Volume in 1 second (FEV1.0), Percent Predicted FEV1.0, and FEV1.0/Forced Vital Capacity (FVC) ratio in the patients were significantly low as compared with the control subjects. The FEV1.0/FVC ratio was negatively correlated with the Lund-Mackay CT scores of the patients with a high CT score. Conclusions: The CRS patients with CC should be investigated with lung function. In addition, the multidisciplinary evaluation including a pulmonologist is needed to manage the CRS patients with CC. Level of evidence: Level 4.

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Abstract Objective: To classifying the degree of swallowing impairment in the elderly, comparing clinical and instrumental assessment. Methods: This is a cross-sectional study with quantitative and qualitative analysis of clinical and instrumental assessment of 37 elderly, aged 60 -82 years, of both genders without neurological, oncological or systemic diseases, participated in this study. All participants were submitted to clinical evaluation and their results compared through fiberoptic endoscopic evaluation of swallowing considering liquid, pudding and solid food consistencies. Data were analyzed descriptively and statistically using the analysis of variance test (two-way ANOVA) and Tukey’s post hoc test (p< 0.05). Results: In the clinical evaluation there was a higher occurrence of moderate swallowing impairment, followed by functional swallowing, while in fiberoptic endoscopic evaluation of swallowing the severity of the impairment was greater for moderate and mild degrees. There was no statistical difference between the clinical and instrumental evaluation methods. However, there was a significant interaction between the variables, with a difference for liquid consistency in the instrumental evaluation method. Conclusion: Healthy elderly have different degree of swallowing impairment according to food consistency. The clinical assessment using a scale that considers the physiological changes of the elderly, presented results similar to those found in the instrumental examination. Level of Evidence: 2.

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Abstract Objectives: This study aimed to investigate the effects of an adhesive bone conduction device (aBCD) in children with congenital single-sided deafness (SSD). Specifically, we examined whether the aBCD elicits improvement in the speech perception ability of children with congenital SSD and whether using this device would adversely affect the horizontal localisation abilities of these children. Methods: Thirteen school-aged children with SSD and seven children with Normal Hearing (NH) were included in this study. Speech perception in noise was measured using the Mandarin Speech Test Materials and sound localisation performance was evaluated using broadband noise stimuli (0.5–20 kHz), randomly played from seven loudspeakers at different stimulus levels (65-, 70-, and 75-dB SPL). Results: All children with SSD showed inferior speech perception and sound localisation performance compared with children with NH. The aBCD use remarkably improved the speech perception abilities of these children under quiet and noise conditions; however, their sound localisation abilities neither improved nor deteriorated. Conclusion: This study reveals the effectiveness and safety of a non-surgical aBCD in paediatric patients with SSD. Our results provide a theoretical basis for early hearing intervention with an aBCD in children with congenital SSD who are temporarily unable to undergo ear surgery. Level of evidence: Level 3.

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Abstract Objective: This is a retrospective analysis of the major and minor complications of cochlear implants, as well as the Risk Factors (RF) involved. Methods: We analyzed the medical records of patients submitted to cochlear implants at public University from 2006 to July 2019, and list here the major and minor complications found, and their risk factors. Results: There were 193 ears, 100 (51.3%) from females and 93 (48.2%) from males, with a mean age of 23.63 years. In 54 of them (28%), there were alterations seen in the Temporal Bone CT scan, and 44 (22.8%) in the brain MRI. There were 158 (81.9%) insertions performed; 127 (65.8%) of them through the round window. There were 78 complications: 19 (9.8%) major and 56 (29%) minor complications. Among the major complications, there were 3 (1.6%) Surgical Site infections (SS); 5 (2.6%) hematomas/seromas; 5 (2.6%) electrode extrusion; 5 (2.6%) device faults; 1 (0.5%) wrong path. Among the minor complications, there were 6 (3.1%) Acute Otitis Media (AOM); 9 (4.7%) SS infections; 4 (2.1%) facial paresis; 17 (8.8%) vertigos; 9 (4.7%) with tinnitus. The most important RF was age. Patients younger than 2.5 years had more major complications: SS infection (p = 0.018) and electrode extrusion (p = 0.017). There was a higher rate of vertigo in adults (p = 0.003), and it was more often associated with comorbidities (p = 0.008). The insertion route, the presence of changes in CT and MRI and the CI brand used did not impact the number of complications. Conclusion: Among the minor complications, those involving the vestibular system were the most common, especially in adults with comorbidities. Regarding major complications, there was an emphasis on SS infections, hematomas, seromas, electrode extrusion, especially in children under two years of age. There were implanted device faults (2.6%), with none of the brands evaluated standing out.

Resumo em Inglês:

Abstract Objective(s): Endoscopic thyroidectomy, such as axillary, areola and transoral approaches, offer the advantage of a good cosmetic outcome, but it requires a wider dissection field compared to open thyroidectomy. Recently, chest-collarbone approach thyroidectomy has been widely developed in China because of its shorter anatomical route compared to other endoscopic approaches. This study retrospectively evaluated endoscopic thyroidectomy via chest-collarbone approach in patients with thyroid nodules to determine its feasibility. Methods: A total of 46 patients with thyroid disease who underwent endoscopic thyroidectomy between January 2022 and December 2022 were enrolled in the study and randomly matched to patients with thyroid disease who underwent open thyroidectomy at the same time based on nodule size and pathology. Postoperative bleeding, hoarseness situation, hospital stay, postoperative drainage volume, laryngeal nerve palsy, hypoparathyroidism and wound infection were assessed in both groups. Results: Forty-four patients underwent endoscopic thyroidectomy successfully and two patients changed to open thyroidectomy. The amount of postoperative drainage for the endoscopic thyroidectomy group was 102.78 ± 28.04 mL, and which was 71.91 ± 19.20 for open thyroidectomy group (p < 0.001). The postoperative hospital stay for the endoscopic thyroidectomy group was 8.78 ± 2.57 days, and which was 7.22 ± 1.13 for open thyroidectomy group (p < 0.001). There was no significant difference in postoperative bleeding, hoarseness situation, and wound infection between the two groups. Laryngeal nerve palsy, supraclavicular nerve injury and hypoparathyroidism were not observed in any patient during this study. Conclusion: Chest-collarbone endoscopic thyroid surgery is acceptable. This treatment improves in a good cosmetic outcome in patients with thyroid disease. To assess patients with preoperative nodule size and nature of the case is the impact of the success rate, which is particularly important.

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Abstract Objective: This study aimed to use validated measures to evaluate the functional and esthetic outcomes in patients who underwent functional rhinoplasty for Internal Nasal Valve Dysfunction (INVD) in Korea. Methods: A retrospective review of consecutive patients who underwent functional rhinoplasty for INVD confirmed by endoscopic findings and the modified Cottle test between 2016 and 2018 was performed. Nasal obstruction was assessed with the Visual Analog Scale (VAS) and nasal obstruction symptom evaluation (NOSE) scale. Acoustic rhinometry was performed pre- and post-operatively. The Minimal Cross-Sectional Area (MCA) of the nose was measured. Objective assessment of the esthetic outcomes was performed with the Objective Rhinoplasty Outcome Score (OROS), which assesses tip rotation, projection, width, dorsal height, width, length, symmetry, and the overall result. Results: Fifty-seven patients (46 men and 11 women; mean age, 30.5 ± 12.3 years) who underwent functional rhinoplasty were included in this study. The VAS and NOSE scores indicated functional improvement in all cases (all p<0.001). There were no significant between-group differences (VAS score, p = 0.274; NOSE score, p = 0.952). The objective functional outcomes evaluated using MCA on the concave (p = 0.478) and convex (p = 0.631) sides did not differ significantly pre- and post-operatively. The subjective evaluation of esthetic satisfaction revealed no between-group difference. Moreover, 31 out of 44 patients (70.5%) with static INVD and nine out of 14 patients (64.3%) with dynamic or combined INVD showed excellent outcomes. Regarding objective esthetic outcomes, scores for the eight factors were >3, and there was no significant difference between the two groups (all p> 0.05). Conclusions: Functional rhinoplasty, including extracorporeal septoplasty and spreader grafting, may be a viable option for correcting INVD with functional and esthetic improvement. Dynamic INVD is less prevalent among Asians, and there was no significant difference in the surgical outcomes compared with those of static INVD. Level of Evidence: Level 4.

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Abstract Objective: The purpose was to explore the effects of traditional and non-traditional lipid parameters on Sudden Sensorineural Hearing Loss (SSNHL). Methods: The study included 452 patients diagnosed with SSNHL, among whom 206 patients had a level of hearing improvement ≥10dB after one month of follow-up. A propensity score-matched (2:1) control group was used. Conditional and unconditional logistic regression were used to analyze the risk factors for SSNHL. Results: Patients with SSNHL had a higher risk of concomitant hypertension and elevated atherosclerogenic lipid levels, with apolipoprotein B and apolipoprotein E identified as independent risk factors for the onset of SSNHL. Additionally, the Lipid Comprehensive Index (LCI) was an independent risk factor for the degree of hearing loss. A positive linear correlation was revealed between triglyceride, non-high-density lipoprotein cholesterol, atherogenic index, Castelli risk index, atherogenic index of plasma, LCI and hearing loss. However, no linear relationship was observed between hearing gain and any lipid parameters. When Total Cholesterol (TC) was in the range of borderline high, the treatment effect was the best. However, the statistical significance disappeared upon adjusting for confounding factors. Conclusion: Patients with SSNHL exhibited markedly dysregulated lipid metabolism. Elevated serum lipid levels may be a causative factor in auditory impairment and can influence the extent of hearing loss. Promptly improving cochlear microcirculation may benefit patients with borderline elevated TC. Level of evidence: 4.

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Abstract Objectives: Identifying voice handicap and voice-related quality of life in patients presenting pulmonary impairment associated with COVID-19 infection, comparing pulmonary parameters between these patients and individuals in the control group, as well as correlating pulmonary parameters to self-assessment questionnaires (IDV-10 and QVV). Methods: Thirty-five (35) patients presenting pulmonary impairment with COVID-19 infection were herein selected and compared to 35 individuals who were not affected by COVID-19 infection. Two self-assessment questionnaires were applied (vocal handicap index and voice quality of life protocol). Maximum phonation time Forced Expiratory Pressure (PEF) and Forced Inspiratory Pressure (PIF) were measured and videolaryngoscopy was performed. Results: There was statistically significant difference in scores recorded in voice self-assessment questionnaires (IDV-10 and QVV), Expiratory Pressure (PEF) and Forced Inspiratory Pressure (PIF) between patients with pulmonary impairment associated with COVID-19 infection and those in the control group. Correlation between PEF/PIF and scores recorded in voice self-assessment questionnaires was also observed. Conclusion: Pulmonary impairment associated with COVID-19 infection has worsened voice handicap and voice-related quality of life in the assessed patients, as well as reduced their forced expiratory and inspiratory pressure in comparison to the control group. Level of evidence: 4.

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Abstract Objective: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. Methods: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. Results: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. Conclusions: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. Level of evidence: How common is the problem? Level 2. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1. What will happen if we do not add a therapy? (Prognosis) Level 1. Does this intervention help? (Treatment Benefits) Level 1. What are the COMMON harms? (Treatment Harms) Level 1. What are the RARE harms? (Treatment Harms) Level 1. Is this (early detection) test worthwhile? (Screening) Level 1I.

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Abstract Objectives: To describe the occurrence of post-extubation laryngitis, analyze its one-year evolution, and correlate laryngeal lesions with clinical outcomes. Methods: Retrospective study including children up to 13 years old at a tertiary hospital between March 2020 and March 2022 with diagnosis of post-extubation laryngitis confirmed by endoscopic examination. Exclusion criteria were prior history of intubation or anatomical airway abnormalities. Medical records were reviewed to characterize patients, underlying diagnosis, laryngeal lesions, treatment, and outcomes at 12-month follow-up. Results: The study included 38 endoscopically confirmed post-extubation laryngitis cases, corresponding to 86.4% of suspected cases. The mean age was 13.24 months, and 60.5% were male. Acute respiratory failure was the leading cause of intubation. Initial treatment was clinical, and initial diagnosis was defined by nasopharynoglaryngoscopy and/or Microlaryngoscopy and Bronchoscopy (MLB) findings. Initial diagnostic MLB was performed in 65.7% of the patients. Approximately half (53%) of the patients exhibited moderate or severe laryngeal lesions. When compared to mild cases, these patients experienced a higher rate of extubation failures (mean of 1.95 vs. 0.72, p = 0.0013), underwent more endoscopic procedures, and faced worse outcomes, such as the increased need for tracheostomy (p = 0.0001) and the development of laryngeal stenosis (p = 0.0450). Tracheostomy was performed in 14 (36.8%) children. Patients undergoing tracheostomy presented more extubation failures and longer intubation periods. Eight (21%) developed laryngeal stenosis, and 17 (58.6%) had complete resolution on follow-up. Conclusion: Post-extubation laryngitis is a frequent diagnosis among patients with clinical symptoms or failed extubation. The severity of laryngeal lesions was linked to a less favorable prognosis observed at one-year follow-up. Otolaryngological evaluation, follow-up protocols, and increased access to therapeutic resources are essential to manage these children properly. Level of evidence: Level 4.

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Abstract Objective: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. Methods: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. Results: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. Conclusion: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives forCRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS. © 2024 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).